Weight regain after a successful weight loss intervention is very common. Most studies show that, on average, the weight loss attained during a weight loss intervention period is not or is not fully maintained during follow-up. We review what is currently known about dietary strategies for weight loss maintenance, focusing on nutrient composition by means of a systematic review and meta-analysis of studies and discuss other potential strategies that have not been studied so far. Twenty-one studies with 2875 participants who were overweight or obese are included in this systematic review and meta-analysis

1. nutrients
Review
Dietary Strategies for Weight Loss Maintenance
Marlene A. van Baak * and Edwin C. M. Mariman
Department of Human Biology, NUTRIM School for Nutrition and Translation Research in Metabolism,
Maastricht University, 6229 ER Maastricht, The Netherlands
* Correspondence: m.vanbaak@maastrichtuniversity.nl
Received: 25 June 2019; Accepted: 12 August 2019; Published: 15 August 2019
Abstract: Weight regain after a successful weight loss intervention is very common. Most studies
show that, on average, the weight loss attained during a weight loss intervention period is not
or is not fully maintained during follow-up. We review what is currently known about dietary
strategies for weight loss maintenance, focusing on nutrient composition by means of a systematic
review and meta-analysis of studies and discuss other potential strategies that have not been studied
so far. Twenty-one studies with 2875 participants who were overweight or obese are included in
this systematic review and meta-analysis. Studies investigate increased protein intake (12 studies),
lower dietary glycemic index (four studies), green tea (three studies), conjugated linoleic acid (three
studies), higher fibre intake (three studies), and other miscellaneous interventions (six studies).
The meta-analysis shows a significant beneficial effect of higher protein intake on the prevention of
weight regain (SMD (standardized mean difference) −0.17 (95% CI −0.29, −0.05), z = 2.80, p = 0.005),
without evidence for heterogeneity among the included studies. No significant effect of the other
strategies is detected. Diets that combine higher protein intake with different other potentially
beneficial strategies, such as anti-inflammatory or anti-insulinemic diets, may have more robust
effects, but these have not been tested in randomized clinical trials yet.
Keywords: weight regain; obesity; diet composition; protein intake; systematic review and
meta-analysis
1. Introduction
Over the past decades, many studies have been performed to gain insight into the best dietary
strategy to lose weight. It turns out that there is probably not one best strategy and that individual
preferences can be taken into account as long as the individual adheres to the diet and energy restriction
is attained [1,2].
A much less studied topic is what the best dietary strategy is to prevent weight regain after
successful weight loss. Weight regain after a successful weight loss intervention is very common.
Indeed, most studies show that, on average, the weight loss attained during a weight loss intervention
period is not or is not fully maintained during follow-up [3,4]. However, the amount of weight regain
differs among studies, and there are also large inter-individual differences in weight regain within
studies (e.g., see [5]). Although it is often stated that weight regain is inevitable, still, a considerable
number of individuals are able to maintain some weight loss over longer periods of time. For instance,
Coughlin et al. (2016) [6] reported that after an initial weight loss of 8 kg over a 6-month period,
participants of the Weight Loss Maintenance trial maintained a 4 kg weight loss after 2 years of
follow-up and maintained a 3 kg weight loss after 5 years. Pekkarinen et al. (2015) [7] found that
35% of the participants of a 4-month weight loss intervention maintained a weight loss ≥ 5% after
2 years follow-up. In the Diabetes Prevention Outcome Study, it was found that 40% of the participants
who had lost ≥ 5% of their initial body weight after 1 year (in the intensive lifestyle group) had
Nutrients 2019, 11, 1916; doi:10.3390/nu11081916 www.mdpi.com/journal/nutrients

2. Nutrients 2019, 11, 1916 2 of 12
maintained at least 5% weight loss after 15 years of follow-up [8]. On average, no weight regain during
a follow-up period of 12 months was reported after a weight loss program of 3 months in a Japanese
worksite intervention [9]. In the Look Ahead Study, comparing an intensive lifestyle intervention
(ILI) with regular diabetes control, weight regain occurred after 1 year, but at 4 years weight loss was
still significantly more pronounced in the ILI group, as was the case after 8 years (ILI −4.7%, control
−2.1%) [10,11]. Thus, although weight regain is a common phenomenon, a considerable proportion of
the participants in structured weight loss interventions are able to maintain a certain amount of weight
loss over a prolonged period of time. Potential mechanisms that explain the tendency for weight loss
regain and the inter-individual differences are currently being studied in the hope to develop improved
(and more personalized) strategies for the prevention of weight regain.
Here, we will review what is currently known about dietary strategies for weight loss maintenance,
focusing on nutrient composition, by means of a systematic review and meta-analysis of studies.
Furthermore, we will discuss other dietary strategies that have not been studied yet, but that may be
worth investigating based on underlying mechanisms.
2. Systematic Review and Meta-Analysis of Dietary Strategies for Weight Loss Maintenance
2.1. Methods
2.1.1. Search Strategy and In-/Exclusion Criteria
We conducted a systematic literature search on dietary strategies that have been studied in the
context of weight loss maintenance in adults who were overweight or obese. Search terms in PubMed
were ((weight regain) or (weight maintenance) or (weight loss maintenance)) and diet, with filters:
clinical trial, humans. The search yielded 1062 articles. Based on title and abstract and the in- and
exclusion criteria below, 46 studies were selected for further scrutiny of the text. Studies were included
if participants were adults, were overweight or obese at baseline, and had been randomized to different
diets after following the same energy-restricted diet to attain weight loss, and if the randomized diets
were ad libitum and the study design was a randomized controlled trial (RCT). Outcome was the
weight change over the experimental period. Seven studies were excluded because they were not ad
libitum; six were no RCT, eight had no weight loss phase before randomization, two reported no or
incomplete outcomes, one study had no appropriate control, and one study was a review. Therefore,
21 studies were included in this systematic review and meta-analysis.
2.1.2. Data Extraction
Data extracted from each study included the following items: first author, year of publication, initial
BMI, initial weight loss, sample size, type of intervention, study duration, pre- and post-intervention
body weight, or weight change plus measure of variation standard deviation (SD), standard error of
the mean (SE), or confidence interval (CI) in the experimental and the control group.
2.1.3. Quality Assessment
Quality of the selected studies and risk of bias was assessed with the risk of bias checklist (RoB 2.0)
from the Cochrane Collaboration using Review Manager 5.3 software (The Nordic Cochrane Centre,
The Cochrane Collaboration, Copenhagen, Denmark, 2014).
2.1.4. Data Synthesis and Statistical Analysis
To calculate the effect size of each study, we used the mean change and SD of body weight over
the experimental period in the control and intervention groups. If these values were not reported, we
calculated the mean difference as the difference in mean body weight pre and post treatment and its
SD using the formula: SD = square root ((SDpretreatment)2 + (SDposttreatment)2) − (2r × SDpretreatment ×

3. Nutrients 2019, 11, 1916 3 of 12
SDposttreatment). Because the pretest–posttest correlation coefficients (r) were not reported in the studies,
an r value of 0.5 was assumed throughout.
The meta-analysis of included studies was conducted using the publicly available Cochrane Review
Manager 5.3 software (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark,
2014). If a study included more than two experimental groups, which were compared with one control
group, the number of subjects in the control group was divided by the number of comparisons. The effect
size was expressed as standardized mean difference (SMD), because not all studies reported the outcome
in kg; in some %, weight loss was reported. For comparability, data from the completers analysis were
used for the meta-analysis. Dropout was often high (20%), and methods used to statistically correct for
dropout were diverse and often arbitrary (e.g., last-observation-carried-forward, return-to-baseline).
Random-effects models were used for the statistical analysis. Heterogeneity was assessed using
the I2 index. The effect size is reported as the standardized mean difference with its 95% confidence
interval (CI). A p-value 0.05 is considered statistically significant.
2.1.5. Publication Bias
Publication bias was assessed by visual inspection of the funnel plots.
2.2. Results
An overview of the characteristics of the 21 included studies is given in Table 1. Of the 21
included studies, eight studies (with a total of 12 intervention arms) (intervention n = 664, control
n = 504) examined the effect of increasing protein intake on weight loss maintenance [12–19]. The other
studies reported on other dietary strategies (lowering of glycemic index, three studies (intervention
n = 254, control n = 223) [12,17,20]; green tea or its component epigallocatechin-3-gallate (EGCG)
supplementation, three studies (intervention n = 93, control n = 93) [15,21,22]; whole grain enriched diet
or fibre supplementation, two studies (intervention n = 101, control n = 99) [23,24]; conjugated linoleic
acid (CLA) supplementation, two studies (intervention n = 78, control n = 77) [25,26]. The remainder of
the studies reported on miscellaneous interventions: mono-unsaturated, fat-enriched diet, one study with
short or long-term follow-up [27,28]; low-fat diet, one study with short or long-term follow-up [27,28];
acarbose supplementation, one study [29]; capsaicin supplementation, one study [30]; gamma-linoleic
acid (GLA) supplementation, one study [31]; and CHO supplementation without or with a mixture of
chromium picolinate, soluble fibre, and caffeine, one study [32] (intervention n = 274, control n = 177).
Figure 1 shows the Forest plots for the included studies per type of dietary intervention. For the
protein studies, the SMD was −0.17 (95% CI −0.29, −0.05). The test for the overall effect was significant
(p = 0.005), with no evidence for heterogeneity among the included studies (I2 = 0%), suggesting that
an increased protein content of an ad libitum diet has a beneficial effect on weight loss maintenance.
The effect size was modest: the mean difference in weight change across studies was −1.02 kg (95% CI
−1.77, −0.28). However, approximately half of the weight regain was, on average, prevented in these
studies, with durations between 3 and 12 months. Since the study by Aller et al. (2014) [12] was a substudy
(12 month results in part of the study centres) of the Diogenes trial reported in Larsen et al. (2010) [17]
(6 months results in all centres), the outcomes are not completely independent. However, leaving out the
study by Aller et al. [12] does not change the result of the analysis (SMD −0.14 (95% CI −0.27, −0.02) (p
= 0.03). In three of the studies, participants were given dietary advice to increase protein intake by 10
to 15 energy % without specific attention to the protein source (Aller, Debridge, Larsen). In three other
studies, protein intake was increased by supplementation (two studies with casein (30 and 48 g/day)
(Lejeune, Westerterp-Plantenga) and one study with whey or soy (45 g/day) (Kjølbaek). In the remaining
two studies (Claessens, Hursel), a combination of casein supplementation (50 g/day) and dietary advice
was used. Potential mechanisms that have been suggested for the beneficial effect of a higher protein
intake are the satiating properties of protein, their thermogenic effect, and their effect on fat free mass
maintenance/increase [33]. Whether the changes in gut microbiota that are seen with higher protein intake
also play a role or whether they are potentially harmful remains to be established [34].

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Table 1. Characteristics of the randomized clinical trials evaluating the effect of dietary strategies on weight loss maintenance that have been included in the
systematic review.
Author Year Country Participants Intervention Characteristics Main Conclusion Authors
Total
Number
Sex Age
Diagnostic
Criteria
Diet Duration
Dropout n
(%)
Aller 2014
Netherlands
and Denmark
256
40%
male
27–59
year
BMI ≥ 27
kg/m2
five diet groups: lower
protein/lower glycemic index
(GI); higher protein/lower GI;
lower protein/higher GI; higher
protein/higher GI; control
12 months 117 (45%)
higher protein content
improves weight loss
maintenance
Bajerska 2015 Poland 55
men and
women #
49–65
year
BMI 30–50
kg/m2
rye bread with green tea extract
vs. rye bread
12 weeks 0 (0%)
green tea consumption did not
improve weight loss
maintenance
Claessens 2009 Netherlands 5
35%
male
30–60
year
BMI ≥ 27
kg/m2
High-protein plus whey or
casein supplements vs.
high-carbohydrate plus
maltodextrin supplements
12 weeks 6 (11%)
low-fat, high-casein, or
high-whey protein diets are
more effective for weight loss
maintenance than low-fat,
high-carbohydrate diets
Delbridge 2009 Australia 141
50%
male
18–75
year
BMI ≥ 27
kg/m2
higher protein vs. lower
protein diet
12 months 59 (42%)
the protein or carbohydrate
content of the diet had no effect
on weight loss maintenance
Due 2008 Denmark 131
42%
male
18–35
year
BMI ≥ 28
kg/m2
high-MUFA vs. low-fat vs.
control diet
6 months 25 (19%)
diet composition had no major
effect on preventing weight
regain
Due 2017 Denmark 131
42%
male
18–35
year
BMI ≥ 28
kg/m2
high-MUFA vs. low-fat vs.
control diet
18 months 58 (44%)
weight regain did not differ
among the diets
Hauner 2001 Germany 110
20%
male
21–66
year
BMI 32–38
kg/m2 acarbose vs. placebo capsules 26 weeks 35 (32%)
no benefit of acarbose to
stabilise weight reduction
Hursel 2009 Netherlands 80
men and
women #
18–60
year
BMI 25–35
kg/m2
high-protein diet plus
EGCG/caffeine vs. high-protein
diet plus placebo vs.
normal-protein diet plus
EGCG/caffeine vs. normal
-protein diet plus placebo
13 weeks 0 (0%)
both EGCG/caffeine and higher
protein improved weight
maintenance independently
Kamphuis 2003 Netherlands 60
43%
male
20–50
year
BMI 25–30
kg/m2
conjugated linoleic acid (CLA)
low dose vs. placebo and CLA
high dose vs. placebo
13 weeks 6 (10%)
CLA did not result in improved
weight loss maintenance

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Table 1. Cont.
Author Year Country Participants Intervention Characteristics Main Conclusion Authors
Kjølbaek 2017 Denmark 189
men and
women #
18–60
year
BMI 28–40
kg/m2
whey supplement vs. whey
plus calcium supplement vs.
soy supplement vs. placebo
(maltodextrin)
24 weeks 38 (20%)
protein supplementation did
not result in improved weight
maintenance
Kovacs 2004 Netherlands 104
men and
women #
18–60
year
BMI 25–35
kg/m2 green tea vs. placebo capsules 13 weeks 0 (0%)
weight maintenance not
affected by green tea
Kristensen 2017 France 178 women
20–50
year
BMI 27–34
kg/m2
whole grain vs. refined grain
foods
12 weeks 9 (5%)
no effect of whole grain on
weight maintenance, but
dietary adherence was low
Larsen 2010
Eight European
countries
773
men and
women #
18–65
year
BMI 27–45
kg/m2
five diet groups: lower
protein/lower GI; higher
protein/lower GI; lower
protein/higher GI; higher
protein/higher GI; control
26 weeks 225 (29%)
higher protein content and
lower GI improve maintenance
of weight loss
Larsen 2006 Denmark 101
men and
women #
18–65
year
BMI 28–35
kg/m2
conjugated linoleic acid (CLA)
or placebo capsules
52 weeks 24 (24%)
CLA supplementation does not
prevent weight regain
Lejeune 2003 Netherlands 91
men and
women #
18–60
year
BMI 25–35
kg/m2 capsaicin vs. placebo capsules 12 weeks 0 (0%)
capsaicin had no limiting effect
on weight regain
Lejeune 2005 Netherlands 103
men and
women #
18–60
year
BMI 25–35
kg/m2
protein supplement vs. control
(no placebo)
6 months 0 (0%)
a higher protein intake
improved weight maintenance
Pasman 1997 Netherlands 39 women
41 ± 7
year
obese
fibre supplement vs. control
(no placebo)
14 months 8 (20%)
no effect of fibre
supplementation on weight
maintenance
Pasman 1997 Netherlands 39 women
35 ± 7
year
obese
CHO plus
chromium-picolinate plus fibre
plus caffeine supplementvs.
CHO supplement vs. control
(no placebo)
14 months 6 (15%)
CHO supplementation
beneficial for weight
maintenance, no additional
effect of
chromium-picolinate/fibre/caffeine
Philippou 2008 UK 42 * ?
18–65
year
BMI 27–45
kg/m2 higher GI vs. lower GI diet 4 months ?
changing the diet GI does not
affect weight maintenance
Schirmer 2007 USA 50 9% male
mean
~50 year
BMI after
weight loss
34 kg/m2
gamma-linolenate (GLA) vs.
placebo capsules
12 months 20 (40%) **
GLA reduced weight regain
after major weight loss
Westerterp-Plantenga
2004 Netherlands 148
men and
women #
44 ± 10
year
BMI 25–35
kg/m2
protein supplement vs. control
(no placebo)
13 weeks 0 (0%)
higher protein intake resulted
in lower body weight regain
# did not report numbers of men and women separately; * number refers to completers; ** due to early termination.

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Figure 1. Forest plots of dietary strategies for the prevention of weight regain after weight loss. The
box size is proportional to the weight contributed by the study to the combined study mean.
Horizontal lines span individual study 95% confidence intervals (CI). Diamonds represent the
combined study standardized mean value and the corresponding 95% CI values.
The meta-analysis of studies on the lowering of the glycemic index of the diet shows an SMD of
−0.07 (95% CI −0.43, 0.28) (p = 0.68), but with high heterogeneity (I2 = 69%). This heterogeneity is
clearly due to the study by Aller et al. (2014) [12]. When this study is left out of the analysis, the SMD
is −0.23 (95% CI −0.45, −0.02) (p = 0.03) and the mean difference is −1.09 kg (95% CI −2.06, −0.13). The
study by Aller et al. had the longest follow-up (12 months), compared to 4 and 6 months in the other
two studies (Philippou et al. 2009 [20] and Larsen et al. 2010 [17], respectively), and changes in dietary
adherence over time may play a role. As it is, the picture is not yet clear for the potential effectiveness
of low glycemic diets for prevention of weight regain, and more studies are needed. The interventions
with green tea, conjugated linoleic acid, and fibre so far do not show an effect on prevention of weight
regain, without evidence for heterogeneity. The same holds for the miscellaneous studies, although
these are, of course, hard to compare.
Figure 1. Forest plots of dietary strategies for the prevention of weight regain after weight loss. The box
size is proportional to the weight contributed by the study to the combined study mean. Horizontal
lines span individual study 95% confidence intervals (CI). Diamonds represent the combined study
standardized mean value and the corresponding 95% CI values.
The meta-analysis of studies on the lowering of the glycemic index of the diet shows an SMD
of −0.07 (95% CI −0.43, 0.28) (p = 0.68), but with high heterogeneity (I2 = 69%). This heterogeneity
is clearly due to the study by Aller et al. (2014) [12]. When this study is left out of the analysis, the
SMD is −0.23 (95% CI −0.45, −0.02) (p = 0.03) and the mean difference is −1.09 kg (95% CI −2.06, −0.13).
The study by Aller et al. had the longest follow-up (12 months), compared to 4 and 6 months in the
other two studies (Philippou et al. 2009 [20] and Larsen et al. 2010 [17], respectively), and changes
in dietary adherence over time may play a role. As it is, the picture is not yet clear for the potential
effectiveness of low glycemic diets for prevention of weight regain, and more studies are needed.
The interventions with green tea, conjugated linoleic acid, and fibre so far do not show an effect on
prevention of weight regain, without evidence for heterogeneity. The same holds for the miscellaneous
studies, although these are, of course, hard to compare.

7. Nutrients 2019, 11, 1916 7 of 12
The risk of bias analysis of the individual studies is shown in Figure 2. In general, most studies
were of acceptable quality, although in many studies information about one or more aspects was
missing, which resulted in ‘unclear bias’ grading. In diet interventions, not using supplement blinding
of participants and study personnel is often not possible, and these studies were therefore graded
as ‘unclear bias’ with respect to performance and detection bias. In some of the supplementation
studies, no placebo supplement was included, also resulting in an unclear risk of performance and
detection bias qualification. Attrition rate was considerable in many studies, and reasons for dropout
and distribution across intervention groups were sometimes not reported. This resulted in ‘unclear
bias’ qualification with respect to attrition bias. Lack of trial registration resulted in ‘unclear bias’
qualification with respect to selective reporting bias. A summary of the risk of bias analysis is shown
in Figure 3. Visual inspection of the funnel plot of the protein studies (Figure 4) showed no evidence
for publication bias. Similar results were found for the other intervention types.
Nutrients 2019, 11, x FOR PEER REVIEW 2 of 12
The risk of bias analysis of the individual studies is shown in Figure 2. In general, most studies
were of acceptable quality, although in many studies information about one or more aspects was
missing, which resulted in ‘unclear bias’ grading. In diet interventions, not using supplement
blinding of participants and study personnel is often not possible, and these studies were therefore
graded as ‘unclear bias’ with respect to performance and detection bias. In some of the
supplementation studies, no placebo supplement was included, also resulting in an unclear risk of
performance and detection bias qualification. Attrition rate was considerable in many studies, and
reasons for dropout and distribution across intervention groups were sometimes not reported. This
resulted in ‘unclear bias’ qualification with respect to attrition bias. Lack of trial registration resulted
in ‘unclear bias’ qualification with respect to selective reporting bias. A summary of the risk of bias
analysis is shown in Figure 3. Visual inspection of the funnel plot of the protein studies (Figure 4)
showed no evidence for publication bias. Similar results were found for the other intervention types.
.
Figure 2. Risk of bias analysis of the individual studies included in the systematic review and meta-
analysis. Green dot = low risk of bias; yellow dot = unclear risk of bias.
Figure 2. Risk of bias analysis of the individual studies included in the systematic review and
meta-analysis. Green dot = low risk of bias; yellow dot = unclear risk of bias.

8. Nutrients 2019, 11, 1916 8 of 12
Nutrients 2019, 11, x FOR PEER REVIEW 3 of 12
Figure 3. Summary of the risk of bias analysis.
Figure 4. Funnel plot of the protein studies included in the meta-analysis. SMD, standardized mean
difference, SE (SMD), standard error of SMD.
3. Other Potential Dietary Strategies for Weight Loss Maintenance
Overall, the meta-analysis of currently published studies on dietary strategies to prevent weight
regain above shows no evidence for a beneficial effect of a number of different dietary interventions
related to glycemic index, fibre, green tea and EGCG, CLA, and miscellaneous other interventions
(high MUFA, low fat, acarbose, capsaicin, a chromium picolinate/fibre/caffeine mixture, and GLA),
except for a beneficial effect of increased protein intake. When interpreting this outcome, it should be
taken into account that the number of studies and the number of participants included addressing
each of these interventions is lower than the number of those related to protein intake. The question
arises whether there are any other strategies that might also be effective but have not been tested so
far with the paradigm of an initial weight loss phase followed by randomization to ad libitum diets
differing in nutrient composition.
We have recently reviewed the adipose-tissue-related mechanisms for weight regain and
discussed strategies for weight loss maintenance based on these mechanisms [35]. One of the
suggested strategies was a diet enriched in omega3-PUFAs, either by omega3-PUFA containing
foods, such as fatty fish, nuts and seeds, and plant oils, or by omega3-PUFA fortified foods or
supplementation. Omega3 fatty acids have multiple potentially beneficial effects. They increase
membrane fluidity, which may reduce cellular stress [36]. Cellular stress in adipocytes may develop
during weight loss when extracellular matrix remodeling is not able to keep track of adipocyte
Figure 3. Summary of the risk of bias analysis.
Nutrients 2019, 11, x FOR PEER REVIEW 3 of 12
Figure 3. Summary of the risk of bias analysis.
Figure 4. Funnel plot of the protein studies included in the meta-analysis. SMD, standardized mean
difference, SE (SMD), standard error of SMD.
3. Other Potential Dietary Strategies for Weight Loss Maintenance
Overall, the meta-analysis of currently published studies on dietary strategies to prevent weight
regain above shows no evidence for a beneficial effect of a number of different dietary interventions
related to glycemic index, fibre, green tea and EGCG, CLA, and miscellaneous other interventions
(high MUFA, low fat, acarbose, capsaicin, a chromium picolinate/fibre/caffeine mixture, and GLA),
except for a beneficial effect of increased protein intake. When interpreting this outcome, it should be
taken into account that the number of studies and the number of participants included addressing
each of these interventions is lower than the number of those related to protein intake. The question
arises whether there are any other strategies that might also be effective but have not been tested so
far with the paradigm of an initial weight loss phase followed by randomization to ad libitum diets
differing in nutrient composition.
We have recently reviewed the adipose-tissue-related mechanisms for weight regain and
discussed strategies for weight loss maintenance based on these mechanisms [35]. One of the
suggested strategies was a diet enriched in omega3-PUFAs, either by omega3-PUFA containing
foods, such as fatty fish, nuts and seeds, and plant oils, or by omega3-PUFA fortified foods or
supplementation. Omega3 fatty acids have multiple potentially beneficial effects. They increase
membrane fluidity, which may reduce cellular stress [36]. Cellular stress in adipocytes may develop
during weight loss when extracellular matrix remodeling is not able to keep track of adipocyte
Figure 4. Funnel plot of the protein studies included in the meta-analysis. SMD, standardized mean
difference, SE (SMD), standard error of SMD.
3. Other Potential Dietary Strategies for Weight Loss Maintenance
Overall, the meta-analysis of currently published studies on dietary strategies to prevent weight
regain above shows no evidence for a beneficial effect of a number of different dietary interventions
related to glycemic index, fibre, green tea and EGCG, CLA, and miscellaneous other interventions
(high MUFA, low fat, acarbose, capsaicin, a chromium picolinate/fibre/caffeine mixture, and GLA),
except for a beneficial effect of increased protein intake. When interpreting this outcome, it should be
taken into account that the number of studies and the number of participants included addressing
each of these interventions is lower than the number of those related to protein intake. The question
arises whether there are any other strategies that might also be effective but have not been tested so
far with the paradigm of an initial weight loss phase followed by randomization to ad libitum diets
differing in nutrient composition.
We have recently reviewed the adipose-tissue-related mechanisms for weight regain and discussed
strategies for weight loss maintenance based on these mechanisms [35]. One of the suggested strategies
was a diet enriched in omega3-PUFAs, either by omega3-PUFA containing foods, such as fatty fish,
nuts and seeds, and plant oils, or by omega3-PUFA fortified foods or supplementation. Omega3 fatty
acids have multiple potentially beneficial effects. They increase membrane fluidity, which may reduce

9. Nutrients 2019, 11, 1916 9 of 12
cellular stress [36]. Cellular stress in adipocytes may develop during weight loss when extracellular
matrix remodeling is not able to keep track of adipocyte shrinking, and may be a signal for refilling of
the adipocyte and thus weight regain [35]. Additionally, omega3-PUFAs are important for a healthy
adipose tissue by improving the metabolic state and reducing the pro-inflammatory state [37,38]. No
effect of increased omega3 fatty acid intake on body weight in individuals with obesity has been found,
although a facilitating effect on weight loss in combination with other weight loss regimens has been
suggested [37]. However, this does not exclude a potential beneficial effect on weight regain in those
individuals that are not able to lower weight loss-induced cellular stress and inflammation in their
adipose tissue.
Polyphenols (e.g., resveratrol, curcumin, green tea components, and (isoflavones) occur naturally
in fruit and vegetables, green tea, black tea, red wine, coffee, chocolate, olives and olive oil, herbs and
spices, nuts, and algae. They may act as anti-oxidants, but also have anti-inflammatory actions and
metabolic effects (e.g., increased fat oxidation [39–41]). As can be concluded from the meta-analysis
above, there is currently no evidence that green tea or its component EGCG has a beneficial effect
on weight loss maintenance. Although there is some evidence for beneficial effects of polyphenols
on body weight gain in experimental animals, the effects on body weight in humans remain to be
determined [39,41,42]. A combination of omega3 fatty acids and polyphenols did not affect body
weight in healthy adolescents [43], but this has not been tested in the context of weight (re)gain.
Another mechanism suggested to play a role in the tendency for weight regain in humans is low
post-weight loss lipolysis [35,44]. Stimulation of lipolysis by capsaicin is not effective [30] (see above).
There also does not seem to be a beneficial effect of CLA supplementation on weight regain [25,26].
CLA is derived from the metabolism of linoleic acid, a poly-unsaturated essential fatty acid, in the
human gut, and is also present in animal products such as meat and dairy. CLA has been shown to
stimulate browning of adipose tissue.
Short chain fatty acids (SCFA) derived from fermentation of dietary fibres by the gut microbiota
have been shown to increase energy expenditure and fat oxidation, but their effect on long-term body
weight regulation in humans is unknown [45]. The microbiota composition, which may be influenced
by dietary means, may affect adipose tissue inflammation and thus potentially be of importance for
body weight regain [46]. A study by Sanchez et al. (2013) found that weight loss was better maintained
in women who consumed a probiotic supplement consisting of Lactobacillus rhamnosus, oligofructose,
and inulin, but no effect was seen in men [47].
Dietary strategies that combine multiple potentially beneficial mechanisms may be a more robust
way forward than single nutrient strategies. Moreover, some strategies may work better in some
individuals than others, depending on preference, which may be important for adherence, but also
on the individual proneness for weight regain and its underlying mechanism, which may differ from
one person to the next. Examples of whole-diet approaches are anti-inflammatory or anti-insulinemic
diets [48]. Both are associated with less weight (re)gain in observational cohort studies [48–50],
but randomized clinical trials are needed to assess their efficacy for prevention of weight (re)gain.
4. Conclusions
Although weight regain after successful weight loss is a major problem in many individuals,
relatively few randomized controlled trials have been performed exploring dietary strategies for more
successful weight maintenance. Our meta-analysis shows that, currently, only diets with increased
protein content have been shown to have a beneficial effect. Diets that combine a higher protein intake
with other potentially beneficial strategies, such as anti-inflammatory or anti-insulinemic diets, may
have more robust effects, but these have not been tested in randomized clinical trials yet.
Author Contributions: Conceptualization, M.A.v.B.; Analysis, M.A.v.B. and E.C.M.M.; Writing—Original Draft
Preparation, M.A.v.B.; Writing—Review Editing, M.A.v.B. and E.C.M.M.
Funding: This research received no external funding.

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